Regional and temporal profiles of c-fos and nerve growth factor mRNA expression in rat brain after lateral cortical impact injury.

Lesion-induced increases in NGF mRNA are thought to be mediated by c-fos gene expression. Conversely, NGF induction of c-fos expression has been reported following administration of exogenous NGF. However, the relationship between c-fos and NGF gene expression after traumatic injury to the intact brain is not known. Thus, we applied in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods to determine temporal profiles of c-fos and NGF mRNA expression in rat brains after controlled impact to the exposed cortex. Using alternate sections from the same rat brains, in situ hybridization studies showed that in neocortex, c-fos mRNA transiently increased at 30 min, 1 hr, and 3 hr after injury, while there were no increases of NGF mRNA at these postinjury time points. In the hippocampus, in situ hybridization showed that c-fos mRNA increased at 30 min, 1 hr and 3 hr postinjury, while NGF mRNA increased at 1 hr, 3 hr but not at 30 min after injury. RT-PCR studies in hippocampus confirmed that c-fos mRNA increased as early as 5 min after injury, peaked at 30 min postinjury, and remained elevated 5 hr postinjury. Levels of hippocampal NGF mRNA expression increased by 1 hr after injury and plateaued until 3 and 5 hr postinjury. These data are consistent with the possible regulatory role of endogenous c-fos on NGF expression following traumatic brain injury.